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SRP093883
Homo sapiens
36 Downloadable Samples
Description
The T lymphoma invasion and metastasis inducing protein 1 (TIAM1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RAC1 and regulates a plethora of functions such as cell proliferation, migration, apoptosis and polarity. Recently, we demonstrated that TIAM1 shuttles between the cytoplasm and nucleus. To determine the nuclear role of TIAM1, we performed RNA-seq on SW620 cells transfected either with a specific pre-validated siRNA for TIAM1 (siTIAM1) or a negative control siRNA (siNT) and generated a list of TIAM1 differentially expressed genes. GSEA revealed significant enrichment among TIAM1-regulated genes for YAP-associated molecular signature. To investigate the interplay of TIAM1 with YAP/TAZ we used RNA-seq, generated a list of YAP/TAZ differentially expressed genes from SW620 cells transfected either with specific siRNAs for YAP/TAZ or a negative control siRNA and compared it with the siTIAM1 RNA-seq dataset. Interestingly, we found that 50% of the TAZ/YAP regulated genes were also TIAM1 dependent. Overall design: mRNA profiles of control, TIAM1 or YAP/TAZ knockdown SW620 cells were generated from three independent experiments using RNA-seq
Publication Title
TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
We examined the effects of TNFa and Spt5, the major DSIF subunit, on nascent and mature transcripts using RNA-Seq of chromatin-associated and cytoplasmic transcripts. Overall design: RNA was extracted from the cytosolic and chromatin fractions of control and Spt5 KD cells that were treated with TNFa for 1 hour
Publication Title
Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
The goal of this study was to determine if fibroblasts from different origin (skin, colon, tumors) were keeping their characteristic while extracted and cultured ex vivo for several passages. HUVEC was used as a control, being cells from a different background. Surprisingly, fibroblasts from different origins are losing their independant characteristic to cluster in a similar way after 5-6 passages in culture in vitro, showing an activated status. Overall design: Fibroblasts were extracted from human skin, colon normal stroma and colon tumor stroma. HUVECs were extracted from human samples at the same time. All cells, each group from 3 different patients, were grown on plastic for 5 passages and mRNA was extracted to perform RNASeq analysis.
Publication Title
Fibroblast surface-associated FGF-2 promotes contact-dependent colorectal cancer cell migration and invasion through FGFR-SRC signaling and integrin αvβ5-mediated adhesion.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 4000
Description
The gene regulatory network in naïve mouse embryonic stem cells (ESCs) must be reconfigured for lineage competence. Tcf3 enables rewiring to formative pluripotency by repressing components of the ESC transcription factor circuitry. However, elimination of Tcf3 only delays, and does not prevent, state transition. Here we delineate distinct contributions of the Ets-family transcription factor Etv5 and the repressor Rbpj. Downstream of Erk1/2 signalling, Etv5 activates enhancers for formative pluripotency. Concomitant up-regulation of Rbpj ensures irreversible exit from the naïve state by extinguishing reversal factors, Nanog and Tbx3. Triple deletion of Etv5, Rbpj and Tcf3 incapacitates ESCs, such that they remain undifferentiated and locked in self-renewal even in the presence of differentiation stimuli. Thus, pluripotency progression is driven hierarchically by two repressors, that respectively dissolve and extinguish the naive network, and an initiator that commissions the formative network. Similar tripartite action may be a general mechanism for efficient cell transitions. Overall design: RNA-seq analysis of parental Rex1-GFPd2 ES cells (RGd2), and deletion mutants generated in this background (Etv5-KO, RbpJ-KO, Etv5-RpbJ-dKO, Etv5-RbpJ-Tcf3-tKO) cultured in 2i, N2B27 or supplemented with Chiron, 3 biological replicates per condition.
Publication Title
Complementary Activity of ETV5, RBPJ, and TCF3 Drives Formative Transition from Naive Pluripotency.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To gain insight into the etiopathogenesis of Multiple sclerosis (MS) we investigated gene expression changes in CD4+ and CD8+ T lymphocytes from monozygotic twins (MZ) discordant for relapsing remitting MS.
Publication Title
CD161(high)CD8+T cells bear pathogenetic potential in multiple sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 96 Downloadable Samples
- Illumina HiSeq 2500
Description
The discovery of significant heterogeneity in the self-renewal durability of adult haematopoietic stem cells (HSCs) has challenged our understanding of the molecules involved in population maintenance throughout life. Gene expression studies in bulk populations are difficult to interpret since multiple HSC subtypes are present and HSC purity is typically less than 50% of the input cell population. Numerous groups have therefore turned to studying gene expression profiles of single HSCs, but again these studies are limited by the purity of the input fraction and an inability to directly ascribe a molecular program to a durable self-renewing HSC. Here we combine single cell functional assays with flow cytometric index sorting and single cell gene expression assays to gain the first insight into the gene expression program of HSCs that possess durable self-renewal. This approach can be used in other stem cell systems and sets the stage for linking key molecules with defined cellular functions. Overall design: single-cell RNA-Seq of haematopoietic stem cells
Publication Title
Combined Single-Cell Functional and Gene Expression Analysis Resolves Heterogeneity within Stem Cell Populations.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Depending on the tumor type IB kinase (IKK) can act as tumor promoter or tumor suppressor in various malignancies. Here we demonstrate a key function of IKK in the suppression of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKK kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of IFN expressing M1-like myeloid cells. In IKK mutant mice M1-like polarization is not controlled in a cell autonomous manner but depends rather on the interplay of both IKK mutant tumor epithelia and immune cells.
Publication Title
IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in MLL-AF9 AML.
Publication Title
KRas(G12D)-evoked leukemogenesis does not require β-catenin.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
West Nile virus (WNV) is the most important cause of endemic encephalitis in the USA. Strikingly, only a small percentage of patients develop clinical disease and of these patients, approximately 1 out of 150 patients develops encephalitis. The basis for this great variability in disease outcome is unknown, but may be related to the innate immune response. Innate immune responses, critical for control of WNV infection, are initiated by signaling through pathogen recognition receptors (PRR) such as RIG-I and MDA5. IPS-1 is a key adaptor in generating a PRR-dependent interferon response.. Here we show that IPS-1 deficiency in hematopoietic cells resulted in increased mortality and delayed WNV clearance from the brain. In IPS-1-/- mice, a dysregulated immune response was detected, characterized by a massive influx of macrophages and virus-specific T cells into the infected brain. These T cells were multifunctional and were able to lyse peptide-pulsed target cells in vitro. However, virus-specific T cells in the infected IPS-1-/- brain exhibited lower functional avidity than those in C57BL/6 brains, possibly contributing to less efficient virus clearance. The presence of virus-specific memory T cells was also not protective. We also show that macrophages were increased in numbers in the IPS-1-/- brain. Both macrophages and microglia exhibited an activated phenotype. Microarray analyses showed the preferential upregulation of genes associated with leukocyte activation and inflammation. Together, these results demonstrate the critical role that hematopoietic cell expression of Type 1 interferon and other IPS-1-dependent molecules have in WNV clearance and in regulating the inflammatory response.
Publication Title
MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Type I interferon-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20 kDa ISG, ISG20, is a nuclear 3''-5''exonuclease with preference for single stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Although the exonuclease activity of ISG20 has been shown to degrade viral RNA in vitro, evidence has yet to be presented that virus inhibition in cells requires this activity. Here, we utilized a combination of an inducible, ectopic expression system and newly generated Isg20-/- mice to investigate mechanisms and consequences of ISG20-mediated restriction. Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus and restricted replication of chikungunya and Venezuelan equine encephalitis viruses. Although restriction by ISG20 was associated with inhibition of translation of infecting genomic RNA, degradation of viral RNAs was not observed. Instead, translation inhibition of viral RNA was associated with ISG20-induced upregulation of over 100 other genes, many of which encode known antiviral effectors. ISG20 modulated the production of IFIT1, an ISG that suppresses translation of alphavirus RNAs. Consistent with this observation, the pathogenicity of IFIT1-sensitive alphaviruses was increased in Isg20-/- mice compared to wild-type viruses, but not in ISG20 ectopic-expressing cells. Our findings establish an indirect role for ISG20 in the early restriction of RNA virus replication by regulating expressionof other ISGs that inhibit translation and possibly other activities in the replication cycle. Overall design: Two clones each of tet-inducible MEFs overexpressing eGFP (control), Isg20, and Isg20(D94G) were induced by tetracycline removal for 72 hours. rRNA was depleted with RiboMinus Eukaryote kit (Life Technologies) and prepared for Illumina directional 100bp paired-end HiSeq2000 reads.
Publication Title
The Interferon-Induced Exonuclease ISG20 Exerts Antiviral Activity through Upregulation of Type I Interferon Response Proteins.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples